title: Indomethacin stimulates glucose production in adults with uncomplicated falciparum malaria.
abstract: In healthy subjects, basal hepatic glucose production is (partly) regulated by paracrine intrahepatic factors. It is unknown if these paracrine factors also influence basal glucose production in infectious diseases with increased glucose production. We compared the effects of 150 mg indomethacin (n = 9), a nonendocrine stimulator of glucose production in healthy adults, and placebo (n = 7) on hepatic glucose production in Vietnamese adults with uncomplicated falciparum malaria. Glucose production was measured by primed, continuous infusion of [6,6-2H2]glucose. After indomethacin, the plasma glucose concentration and glucose production increased in all subjects from 5.3 +/- 0.1 mmol/L to a maximum of 7.1 +/- 0.3 mmol/L (P < .05) and from 17.6 +/- 0.8 micromol x kg(-1) x min(-1) to a maximum of 26.2 +/- 2.5 micromol x kg(-1) x min(-1) (P < .05), respectively. In the control group, the plasma glucose concentration and glucose production declined gradually during 4 hours from 5.4 +/- 0.2 mmol/L to 5.1 +/- 0.1 mmol/L (P < .05) and from 17.1 +/- 0.8 micromol x kg(-1) x min(-1) to 15.1 +/- 1.0 micromol x kg(-1) x min(-1) (P < .05), respectively. There were no differences in plasma concentrations of insulin, counterregulatory hormones, or cytokines between the groups. We conclude that indomethacin administration results in a transient increase in glucose production in patients with uncomplicated falciparum malaria in the absence of changes in plasma concentrations of glucoregulatory hormones or cytokines. Thus, this study indicates that in uncomplicated falciparum malaria, the rate of basal hepatic glucose production is also regulated by paracrine intrahepatic factors.
authors.affiliation: Department of Internal Medicine, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Dekker
authors.forename: J A
authors.initials: JA
authors.lastname: Romijn
authors.lastname: Huynh
authors.forename: M T
authors.initials: MT
authors.lastname: Ackermans
authors.forename: E
authors.initials: E
authors.lastname: Endert
authors.forename: P A
authors.initials: PA
authors.lastname: Kager
authors.forename: L T
authors.initials: LT
authors.lastname: Thuy
authors.forename: H P
authors.initials: HP
authors.lastname: Sauerwein
mesh_terms: D000328:Adult; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D016207:Cytokines / Q000097:blood; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D016778:Malaria, Falciparum / Q000378:metabolism*; D008297:Male
chemical_list: D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D007328:Insulin; D005947:Glucose; D007213:Indomethacin